Amelioration of lipopolysaccharides-induced impairment of fear memory acquisition by alpha-glycosyl isoquercitrin through suppression of neuroinflammation in rats.

Qian Tang, Kazumi Takashima, Wen Zeng, Hiromu Okano, Xinyu Zou, Yasunori Takahashi, Ryota Ojiro, Shunsuke Ozawa, Mihoko Koyanagi, Robert R Maronpot, Toshinori Yoshida, Makoto Shibutani

The Journal of toxicological sciences 2023

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This study investigated the role of neuroinflammation in a lipopolysaccharides (LPS)-induced cognitive dysfunction model in rats using an antioxidant, α-glycosyl isoquercitrin (AGIQ). Six-week-old rats were dietary treated with 0.5% (w/w) AGIQ for 38 days, and LPS at 1 mg/kg body weight was administered intraperitoneally once daily on Days 8 and 10. On Day 11, LPS alone increased or tended to increase interleukin-1β and tumor necrosis factor-α in the hippocampus and cerebral cortex. Immunohistochemically, LPS alone increased the number of Iba1+ and CD68+ microglia, and GFAP+ astrocytes in the hilus of the hippocampal dentate gyrus (DG). AGIQ treatment decreased or tended to decrease brain proinflammatory cytokine levels and the number of CD68+ microglia in the DG hilus. In the contextual fear conditioning test during Day 34 and Day 38, LPS alone impaired fear memory acquisition, and AGIQ tended to recover this impairment. On Day 38, LPS alone decreased the number of DCX+ cells in the neurogenic niche, and AGIQ increased the numbers of PCNA+ cells in the subgranular zone and CALB2+ hilar interneurons. Additionally, LPS alone decreased or tended to decrease the number of synaptic plasticity-related FOS+ and COX2+ granule cells and AGIQ recovered them. The results suggest that LPS administration induced acute neuroinflammation and subsequent impairment of fear memory acquisition caused by suppressed synaptic plasticity of newborn granule cells following disruptive neurogenesis. In contrast, AGIQ exhibited anti-inflammatory effects and ameliorated LPS-induced adverse effects. These results suggest that neuroinflammation is a key factor in the development of LPS-induced impairment of fear memory acquisition.

Citation

Qian Tang, Kazumi Takashima, Wen Zeng, Hiromu Okano, Xinyu Zou, Yasunori Takahashi, Ryota Ojiro, Shunsuke Ozawa, Mihoko Koyanagi, Robert R Maronpot, Toshinori Yoshida, Makoto Shibutani. Amelioration of lipopolysaccharides-induced impairment of fear memory acquisition by alpha-glycosyl isoquercitrin through suppression of neuroinflammation in rats. The Journal of toxicological sciences. 2023;48(3):121-137